BRCC36 is a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. It is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains, and does not have activity toward 'Lys-48'-linked polyubiquitin chains. In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint (1).